Method of operating an analytical laboratory

ABSTRACT

A method of operating an analytical laboratory is presented. The method comprises the steps of: setting a load limit for each laboratory instrument at maximum instrument capacity; dispatching biological samples to laboratory instrument(s) at a dispatch rate not greater than the instrument load limit; each laboratory instrument sending test order queries to the laboratory middleware upon identifying a biological sample; in response to the test order queries transmitting test orders to the laboratory instruments corresponding to the biological samples; the laboratory middleware monitoring a query rate of the plurality of laboratory instruments in order to determine an effective flow rate corresponding to each laboratory instrument; decreasing the load limit of a first laboratory instrument if its effective flow rate is lower than the dispatch rate; increasing the load limit for the first laboratory instrument if its effective flow rate is greater than or equal to the dispatch rate.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.17/082,405, filed Oct. 28, 2020, now U.S. patent Ser. No. 11/313,870,which claims priority to EP 19382952.0, filed Oct. 31, 2019, which arehereby incorporated by reference.

BACKGROUND

The present disclosure generally relates to a computer-implementedmethod of operating an analytical laboratory, in particular an in-vitrodiagnostic laboratory, and to an analytical laboratory configured tocarry out the disclosed method.

In vitro diagnostic testing has a major effect on clinical decisions,providing physicians with pivotal information. In analyticallaboratories, in particular, in-vitro diagnostic laboratories, amultitude of analyses on biological samples are executed by laboratoryinstruments in order to determine physiological and biochemical statesof patients, which can be indicative of a disease, nutrition habits,drug effectiveness, organ function and the like.

According to established laboratory procedures in complex analyticallaboratories, a plurality of instruments process biological samplesaccording to test orders, each test order defining one or moreprocessing steps to be carried out on the biological sample. After thebiological sample has been received and identified by a pre-analyticallaboratory instrument, a laboratory middleware retrieves thecorresponding test orders and determines which instruments are requiredto process the biological sample according to the test order(s). Havingidentified the required instrument(s), the laboratory middlewaredetermines a sample workflow for each sample according to the testorder(s). The sample workflow comprises a sequence and/or timing ofcarrying out the one or more test orders by the one or more analyticalinstruments.

In known analytical laboratories, the laboratory middleware determinesthe sample workflow based on a load limit for each laboratory instrumentbased on a maximum instrument capacity.

The maximum instrument capacity is either set by themanufacturer/provider of the respective instrument or determined basedon historical data reflecting the (average/mean) performance of theinstrument. The load limit, instrument capacity as well as the flow rateof an instrument is defined as the number of biological samples therespective instrument is able to process in a given time frame (e.g.,per hour, per day, etc.). Alternatively, this is referred to asprocessing rate/frequency or instrument throughput and the like

However, it has been observed that the performance of laboratoryinstruments sometimes deviates (significantly) from the maximuminstrument capacity. Such deviations have various causes, such as (un)availability of instrument consumables, degradation/wear of certaincomponents of the instrument; unfavorable environmental conditions;necessity of more frequent calibration/quality control procedures and/oroverloading of the laboratory instruments with biological samples atrates higher than their current capacity.

Degradation in the performance of laboratory instruments and hencedeviations from the assumed instrument capacity leads to situationswhere analytical laboratories operate using the wrong “assumptions” ofinstrument capacity, leading to overloading and/or unfavorable balancingof the load between laboratory instruments. Even if the load limit foreach laboratory instrument is revised on a regular basis, deviations ofthe performance of laboratory instruments may not be reacted upon in atimely manner in known analytical laboratories, potentially leading tooverloading/underutilization of laboratory instruments.

Hence, there is a need for an analytical laboratory and a method ofoperating an analytical laboratory, which preventsoverloading/underutilization of laboratory instruments.

Furthermore, it has been observed that even if one would assume atheoretically perfect load distribution between laboratory instrumentsin an analytical laboratory, without some control of the “input” of theanalytical laboratory as a whole, there would still be a risk that theanalytical laboratory would become overloaded if the inflow ofbiological samples is higher than the overall processing capacity.

Hence, there is a further need for an analytical laboratory and a methodof operating an analytical laboratory wherein an overloading of theanalytical laboratory is prevented.

At a certain point, an overloaded analytical laboratory is unable toreceive additional biological samples. This is particularly problematicwith respect to biological samples which need to be processed urgently(e.g., from emergency care or other situations where e.g., alife-critical decision is dependent on the timely availability of thecorresponding test results).

Therefore, there is an even further need for an analytical laboratoryand method of operating an analytical laboratory, which enables timelyreceipt, and processing of urgent samples, irrespective of overall loadof the analytical laboratory.

SUMMARY

According to the present disclosure, an analytical system and method ofoperating an analytical laboratory comprising a laboratory middlewarecommunicatively connected to a plurality of laboratory instrumentsconfigured to process biological samples is presented. The method cancomprise the steps of setting a load limit by the laboratory middlewarefor each laboratory instrument at a value equal to a maximum instrumentcapacity of the laboratory instrument and dispatching biological samplesby the laboratory middleware to laboratory instrument(s) at a dispatchrate not greater than the instrument load limit. The biological samplescan be dispatched to laboratory instrument(s) configured to carry out atleast one test order corresponding to the biological sample. The methodcan also comprise receiving and identifying biological samples by thelaboratory instruments and sending test order queries by each laboratoryinstrument to the laboratory middleware upon identifying a biologicalsample. The test order query can comprise data identifying thebiological sample. The method can also comprise, in response to the testorder queries, transmitting test orders by the laboratory middleware tothe laboratory instruments corresponding to the biological samplesidentified in the test order queries, monitoring a query rate of theplurality of laboratory instruments by the laboratory middleware inorder to determine an effective flow rate corresponding to eachlaboratory instrument, decreasing the load limit by the laboratorymiddleware of a first laboratory instrument of the plurality oflaboratory instruments if the effective flow rate of the firstlaboratory instrument is lower than the dispatch rate to the firstlaboratory instrument, and increasing the load limit by the laboratorymiddleware for the first laboratory instrument if the effective flowrate of the first laboratory instrument is greater than or equal to thedispatch rate to the first laboratory instrument

Accordingly, it is a feature of the embodiments of the presentdisclosure to address the need for an analytical laboratory and methodof operating an analytical laboratory which preventsoverloading/underutilization of laboratory instruments by determining aneffective flow rate of the laboratory instruments and dynamicallyreacting to the deviations of the effective flow rate by controlling theload limit of each instrument. Other features of the embodiments of thepresent disclosure will be apparent in light of the description of thedisclosure embodied herein.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

The following detailed description of specific embodiments of thepresent disclosure can be best understood when read in conjunction withthe following drawings, where like structure is indicated with likereference numerals and in which:

FIG. 1 illustrates a highly schematic block diagram of the analyticallaboratory according to an embodiment of the present disclosure.

FIG. 2 illustrates a flowchart illustrating a method of operating ananalytical laboratory according to an embodiment of the presentdisclosure.

FIGS. 3A-3B illustrate a set of diagrams illustrating instrumentprocessing rates and load limits according to an embodiment of thepresent disclosure.

FIG. 4A illustrates a first page of a flowchart illustrating thedisclosed methods according to further embodiments of the presentdisclosure.

FIG. 4B illustrates a second page of a flowchart illustrating thedisclosed method according to further embodiments of the presentdisclosure.

FIG. 4C illustrates a third page of a flowchart illustrating thedisclosed method according to further embodiments of the presentdisclosure.

FIG. 4D illustrates a fourth page of a flowchart illustrating thedisclosed method according to further embodiments of the presentdisclosure.

FIG. 5 illustrates a flowchart illustrating an overview of the disclosedmethod of operating an analytical laboratory according to an embodimentof the present disclosure.

FIG. 6 illustrates a highly schematic block diagram of a pre-analyticallaboratory instrument of the disclosed laboratory system according to anembodiment of the present disclosure.

FIG. 7 illustrates a highly schematic block diagram of a pre-analyticallaboratory instrument of the disclosed laboratory system according to anembodiment of the present disclosure.

FIG. 8 illustrates a highly schematic block diagram of an analyticallaboratory instrument of the disclosed laboratory system according to anembodiment of the present disclosure.

FIG. 9 illustrates a highly schematic block diagram of a post-analyticallaboratory instrument of the disclosed laboratory system according to anembodiment of the present disclosure.

DETAILED DESCRIPTION

In the following detailed description of the embodiments, reference ismade to the accompanying drawings that form a part hereof, and in whichare shown by way of illustration, and not by way of limitation, specificembodiments in which the disclosure may be practiced. It is to beunderstood that other embodiments may be utilized and that logical,mechanical and electrical changes may be made without departing from thespirit and scope of the present disclosure.

Certain terms will be used in this patent application, the formulationof which should not be interpreted to be limited by the specific termchosen, but as to relate to the general concept behind the specificterm.

The terms ‘sample’, ‘patient sample’ and ‘biological sample’ can referto material(s) that may potentially contain an analyte of interest. Thepatient sample can be derived from any biological source, such as aphysiological fluid, including blood, saliva, ocular lens fluid,cerebrospinal fluid, sweat, urine, stool, semen, milk, ascites fluid,mucous, synovial fluid, peritoneal fluid, amniotic fluid, tissue,cultured cells, or the like. The patient sample can be pretreated priorto use, such as preparing plasma from blood, diluting viscous fluids,lysis or the like. Methods of treatment can involve filtration,distillation, concentration, inactivation of interfering components, andthe addition of reagents. A patient sample may be used directly asobtained from the source or used following a pretreatment to modify thecharacter of the sample. In some embodiments, an initially solid orsemi-solid biological material can be rendered liquid by dissolving orsuspending it with a suitable liquid medium. In some embodiments, thesample can be suspected to contain a certain antigen or nucleic acid.

The term ‘analyte’ can relate to a component of a sample to be analyzed,e.g., molecules of various sizes, ions, proteins, metabolites and thelike. Information gathered on an analyte may be used to evaluate theimpact of the administration of drugs on the organism or on particulartissues or to make a diagnosis. Thus, ‘analyte’ can be a general termfor substances for which information about presence, absence and/orconcentration is intended. Examples of analytes are e.g., glucose,coagulation parameters, endogenic proteins (e.g., proteins released fromthe heart muscle), metabolites, nucleic acids and so on.

The term ‘analysis or ‘analytical test’ as used herein can encompass alaboratory procedure characterizing a parameter of a biological samplefor qualitatively assessing or quantitatively measuring the presence oramount or the functional activity of an analyte.

The term ‘reagent’ as used herein can refer to materials necessary forperforming an analysis of analytes, including reagents for samplepreparation, control reagents, reagents for reacting with the analyte toobtain a detectable signal, and/or reagents necessary for detecting theanalyte. Such reagents may include reagents for isolating an analyteand/or reagents for processing a sample and/or reagents for reactingwith an analyte to obtain a detectable signal and/or washing reagentsand/or diluents.

The terms ‘sample container’, ‘sample holder’ and ‘sample tube’ canrefer to any individual container for storing, transporting, and/orprocessing a sample. In particular, the term without limitation canrefer to a piece of laboratory glass- or plastic-ware optionallycomprising a cap on its upper end. The container can comprise an openingfor dispensing/aspirating liquid into or out of the vessel. The openingmay be closed by a cap, a breakable seal or like suitable means forclosing the opening in a liquid-tight manner. Sample tubes, e.g., sampletubes used to collect blood, often comprise additional substances suchas clot activators or anticoagulant substances, which can have an impacton the processing of the sample. Consequently, different tube typestypically can be adapted for pre-analytical and analytical requirementsof a particular analysis, e.g., a clinical chemistry analysis, ahematological analysis or a coagulation analysis. A mix up of sampletube types can make samples unusable for analysis. To prevent errors inthe collection and handling of samples, the sample caps of many tubemanufacturers can be encoded according to a fixed and uniform colorscheme. Some sample tubes types, in addition, or alternatively, can becharacterized by particular tube dimensions, cap dimensions, and/or tubecolor. A dimension of a tube can comprises e.g., its height, its sizeand/or further characteristic shape properties. Sample containers can beidentified using identification tag(s) attached thereto. The term‘identification tag’ as used herein can refer to an optical and/or radiofrequency based identifier that allows the identifier tag to be uniquelyidentified by a corresponding identification tag reader.

The ‘identification tag’ shall comprise—but is not limited to—a barcode,a quick response (QR) code or a radio frequency identification (RFID)tag.

The term ‘sample carrier’ as used herein can refer to any kind of holderconfigured to receive one or more sample tubes and configured to be usedfor transporting sample tube(s).

Sample carriers may be of two major types, single holders and sampleracks.

A ‘single holder’ can be a type of sample carrier configured to receiveand transport a single sample tube. Typically, a single holder can beprovided as a puck, i.e., a flat cylindrical object with an opening toreceive and retain a single sample tube.

A ‘sample rack’ can be a type of sample carrier, typically made ofplastics and/or metal, adapted for receiving, holding and transporting aplurality of sample tubes, e.g., five or more sample tubes e.g.,disposed in one or more rows. Apertures, windows or slits may be presentto enable visual or optical inspection or reading of the sample tubes orof the samples in the sample tubes or of a label, such as a barcode,present on the sample tubes held in the sample rack.

The term ‘laboratory instrument’ as used herein can encompass anyapparatus or apparatus component operable to execute one or moreprocessing steps/workflow steps on one or more biological samples and/orone or more reagents. The expression ‘processing steps’ thereby canrefer to physically executed processing steps such as centrifugation,aliquotation, sample analysis and the like. The term ‘instrument’ cancover pre-analytical instruments, post-analytical instruments as well asanalytical instruments.

The term ‘analyzer’/‘analytical instrument’ as used herein can encompassany apparatus or apparatus component configured to obtain a measurementvalue. An analyzer can be operable to determine via various chemical,biological, physical, optical or other technical procedures a parametervalue of the sample or a component thereof. An analyzer may be operableto measure said parameter of the sample or of at least one analyte andreturn the obtained measurement value. The list of possible analysisresults returned by the analyzer can comprise, without limitation,concentrations of the analyte in the sample, a digital (yes or no)result indicating the existence of the analyte in the sample(corresponding to a concentration above the detection level), opticalparameters, DNA or RNA sequences, data obtained from mass spectrometryof proteins or metabolites and physical or chemical parameters ofvarious types. An analytical instrument may comprise units assistingwith the pipetting, dosing, and mixing of samples and/or reagents. Theanalyzer may comprise a reagent-holding unit for holding reagents toperform the assays. Reagents may be arranged for example in the form ofcontainers or cassettes containing individual reagents or group ofreagents, placed in appropriate receptacles or positions within astorage compartment or conveyor. It may comprise a consumable feedingunit. The analyzer may comprise a process and detection system whoseworkflow can be optimized for certain types of analysis. Examples ofsuch analyzers are clinical chemistry analyzers, coagulation chemistryanalyzers, immunochemistry analyzers, urine analyzers, nucleic acidanalyzers, used to detect the result of chemical or biological reactionsor to monitor the progress of chemical or biological reactions.

The term ‘pre-analytical instrument’ as used herein can encompass anyapparatus or apparatus component that can be configured to perform oneor more pre-analytical processing steps/workflow steps comprising—butnot limited to—centrifugation, resuspension (e.g., by mixing orvortexing), capping, decapping, recapping, sorting, tube typeidentification, sample quality determination and/or aliquotation steps.The processing steps may also comprise adding chemicals or buffers to asample, concentrating a sample, incubating a sample, and the like.

The term ‘post-analytical instrument’ as used herein can encompass anyapparatus or apparatus component that can be configured to perform oneor more post-analytical processing steps/workflow steps comprising—butnot limited to—sample unloading, transport, recapping, decapping,temporary storage/buffering, archiving (refrigerated or not), retrievaland or disposal.

The term ‘sample transportation system’ as used herein encompasses anyapparatus or apparatus component that is configured to transport samplecarriers (each holding one or more sample containers) between laboratoryinstruments. In particular, the sample transportation system is a onedimensional conveyor-belt based system, a two-dimensional transportationsystem (such as a magnetic sample carrier transport system) or acombination thereof.

The term ‘laboratory middleware’ as used herein can encompass anyphysical or virtual processing device configurable to control alaboratory instrument/or system comprising one or more laboratoryinstruments in a way that workflow(s) and workflow step(s) can beconducted by the laboratory instrument/system. The laboratory middlewaremay, for example, instruct the laboratory instrument/system to conductpre-analytical, post analytical and analytical workflow(s)/workflowstep(s). The laboratory middleware may receive information from a datamanagement unit regarding which steps need to be performed with acertain sample. In some embodiments, the laboratory middleware might beintegral with a data management unit, may be comprised by a servercomputer and/or be part of one laboratory instrument or even distributedacross multiple instruments of the analytical laboratory. The laboratorymiddleware may, for instance, be embodied as a programmable logiccontroller running a computer-readable program provided withinstructions to perform operations.

A ‘data storage unit’ or ‘database’ can be a computing unit for storingand managing data such as a memory, hard disk or cloud storage. This mayinvolve data relating to biological sample(s) to be processed by theautomated system. The data management unit may be connected to an LIS(laboratory information system) and/or an HIS (hospital informationsystem). The data management unit can be a unit within or co-locatedwith a laboratory instrument. It may be part of the laboratorymiddleware. Alternatively, the database may be a unit remotely located.For instance, it may be embodied in a computer connected via acommunication network.

The term ‘communication network’ as used herein can encompass any typeof wireless network, such as a WiFi™, GSM™, UMTS or other wirelessdigital network or a cable based network, such as Ethernet™ or the like.In particular, the communication network can implement the Internetprotocol (IP). For example, the communication network can comprise acombination of cable-based and wireless networks.

An ‘analytical laboratory’ as used herein can comprise a laboratorymiddleware operatively coupled to one or more analytical; pre- andpost-analytical laboratory instruments wherein the laboratory middlewarecan be operable to control the instruments. In addition, the laboratorymiddleware may be operable to evaluate and/or process gathered analysisdata, to control the loading, storing and/or unloading of samples toand/or from any one of the analyzers, to initialize an analysis orhardware or software operations of the analysis system used forpreparing the samples, sample tubes or reagents for said analysis andthe like. In particular, the instruments of an analytical laboratory andthe laboratory middleware can be interconnected by a communicationnetwork.

A ‘test order’ as used herein can encompass any data object, computerloadable data structure, modulated data representing such data beingindicative of one or more processing steps to be executed on aparticular biological sample. For example, a test order may be a file oran entry in a database. A test order can indicate an analytical test if,for example, the test order can comprise or can be stored in associationwith an identifier of an analytical test to be executed on a particularsample.

A ‘STAT sample’/‘urgent sample’ can be a sample which can need to beprocessed and analyzed very urgently as the analysis result may be oflife-crucial importance for a patient. STAT or urgent samples can beidentified either by data stored on an identifier tag attached to asample container holding the biological sample and/or by data comprisedby and/or associated with the test order indicative of anurgency/priority level of the respective test order. Theurgency/priority level of a test order may be indicated as binary option(e.g., urgent respectively normal) and/or as a scale (e.g., 10 veryurgent, 7 normal, 5 least urgent test order). Additionally, oralternatively, a STAT/urgent sample may be identified by a particulartype of sample container, by a particular type of sample container cap,by a particular color of sample container cap and/or a particulartype/color/format of an identifier tag attached to the sample container.

Embodiments herein disclosed can address the need for an analyticallaboratory and a method of operating an analytical laboratory, which canprevent overloading/underutilization of laboratory instruments bydetermining an effective flow rate of the laboratory instruments anddynamically reacting to the deviations of the effective flow rate bycontrolling the load limit of each instrument.

Embodiments of the disclosed computer implemented method of operating ananalytical laboratory comprising a laboratory middleware communicativelyconnected to a plurality of laboratory instruments configured to processbiological samples can comprise the steps of setting a load limit foreach laboratory instrument at a value equal to a maximum instrumentcapacity of the respective laboratory instrument by the laboratorymiddleware and dispatching biological samples to laboratoryinstrument(s) at a dispatch rate not greater than the instrument loadlimit by the laboratory middleware. The biological samples can bedispatched to those laboratory instrument(s), which can be configured tocarry out at least one test order corresponding to the respectivebiological sample. The method can also comprise the steps of receivingand identifying biological samples by the laboratory instruments and,upon identifying a biological sample, sending test order queries to thelaboratory middleware by each laboratory instrument. The test orderquery(s) comprising data identifying the biological sample. In responseto the test order queries, the laboratory middleware can transmit testorders to the laboratory instruments corresponding to the biologicalsamples identified in the respective test order queries.

According to some embodiments disclosed herein, the laboratorymiddleware can retrieve the test orders corresponding to a biologicalsample from a data storage unit based on said data identifying thebiological sample. The laboratory middleware can monitor a query rate ofthe plurality of laboratory instruments in order to determine aneffective flow rate corresponding to each laboratory instrument.

The query rate can be defined as a number of distinct test order queriesreceived from a particular laboratory instruments in a set period oftime, such as per minute, hour, and so on. Since the laboratoryinstruments send the test queries at a time when they are ready toprocess the biological sample(s), the query rate can be a goodindication of the effective processing capacity of the respectivelaboratory instrument at that time.

If the effective flow rate of the first laboratory instrument is lowerthan the dispatch rate to the first laboratory instrument, thelaboratory middleware can decrease the load limit of a first laboratoryinstrument of the plurality of laboratory instruments. The load limitcan be decreased to ensure that no backlog of unprocessed samplesaccumulates at the laboratory instrument, causing even furtheroverloading of the instrument.

On the other hand, if the effective flow rate of the first laboratoryinstrument is greater than or equal to the dispatch rate to the firstlaboratory instrument, the laboratory middleware can increase the loadlimit for the first laboratory instrument.

Embodiments disclosed herein can be advantageous since adjusting theload limit of laboratory instruments as a reaction to their effectiveflow rate can avoid overloading, or underutilization. Furthermore,determining the effective flow rate by the laboratory middleware basedon the test order queries received from the laboratory instruments canbe advantageous as it can be devoid of any assumptions of performanceand can be implemented even without any change to the existinglaboratory instruments.

According to further embodiments disclosed herein, the laboratorymiddleware can increase or decrease the load limit of the firstlaboratory instrument using continuously modulated control such as, forexample, a proportional-integral-derivative PID, a proportional-integralPI, a proportional-derivative PD, a proportional or an integral controlalgorithm. Such embodiments can be particularly advantageous sincecontinuously modulated control can be configured to keep the effectiveflow rate as close as possible to the maximum instrument capacity,quickly reacting to deviations without overreacting.

In addition to controlling (i.e. increasing or decreasing) the loadlimit, further embodiments disclosed herein can react to deviations ofthe effective flow rate from the dispatch rate by performing loadbalancing between laboratory instruments and/or buffering biologicalsample(s) to temporarily reduce the load on an otherwise overloadedinstrument.

Further embodiments disclosed herein can address the further need for ananalytical laboratory and method of operating an analytical laboratorywherein an overloading of the entire analytical laboratory can beprevented. As mentioned above, even if one would assume a theoreticallyperfect load distribution between laboratory instruments in ananalytical laboratory, without some control of the input of theanalytical laboratory as a whole, there can still be a risk that theanalytical laboratory can become overloaded if the inflow of biologicalsamples is higher than the overall processing capacity. Therefore,embodiments disclosed herein addressing this issue can further comprisethe step of masking one or more of the plurality of laboratoryinstruments, wherein masking can comprise preventing one or more of theplurality of laboratory instruments from receiving biological sample(s),in particular biological sample(s) having at least one associated testorder which the first laboratory instrument is configured to carry out.According to embodiments disclosed herein, preventing one or more of theplurality of laboratory instruments from receiving biological sample(s)can comprise preventing (physically) even the loading of the respectivebiological sample(s) and/or automatically unloading the biologicalsample(s), e.g., into an error output. Such embodiments can beadvantageous as they can limit the inflow of biological samples into theanalytical laboratory, thereby preventing that the overall analyticallaboratory is overloaded, including buffer and archiving capacity of thelaboratory instruments.

Further embodiments disclosed herein can relate to ensuring theanalytical laboratory can still receive and process urgent biologicalsamples while still controlling the overall load of the analyticallaboratory. In order to achieve this, according to further embodiments,masking of laboratory instruments can be performed with respect to alllaboratory instruments, other than one or more laboratory instrumentsreserved for receiving biological samples of high priority.

Referring initially to FIG. 1 , FIG. 1 shows a highly schematic blockdiagram of an embodiment of the disclosed analytical laboratory 1. Asshown on the block diagram of FIG. 1 , embodiments of the disclosedanalytical laboratory 1 for processing biological sample(s) can comprisea plurality of laboratory instruments 10AI, 10PRE, 10POST and alaboratory middleware 20 communicatively connected by a communicationnetwork. The plurality of laboratory instruments 10AI, 10PRE, 10POST canbe configured to execute processing steps on the biological samplesaccording to instructions from the laboratory middleware 20. Alllaboratory instruments 10AI, 10PRE, 10POST can be collectively referredto using the reference numeral 10.

The pre-analytical instruments 10PRE comprised by the analyticallaboratory 1 may be one or more from the list comprising: an instrumentfor centrifugation of samples, a capping-, decapping- or recappinginstrument, aliquoter, a buffer to temporarily store biological samplesor aliquots thereof.

The post-analytical instruments 10POST comprised by the analyticallaboratory 1 may be one or more from the list comprising: a recapper, anunloader for unloading a sample from an analytical system and/ortransporting the sample to a storage unit or to a unit for collectingbiological waste.

According to various embodiments of the disclosed analytical laboratory1, the plurality of laboratory instruments 10AI, 10PRE, 10POST may beidentical or different instruments such as clinical- & immunochemistryanalyzers, coagulation chemistry analyzers, immunochemistry analyzers,urine analyzers, nucleic acid analyzers, hematology instruments and thelike.

The laboratory middleware 20 can be configured to control the analyticallaboratory 1 to carry out the steps of one or more of the methods hereindisclosed and can be communicatively connected to the data storage unit22.

As shown on FIG. 1 , the analytical laboratory 1 can further comprise asample transportation system 10TRS interconnecting the plurality oflaboratory instruments 10AI, 10PRE, 10POST. According to embodimentsdisclosed herein, the sample transportation system 10TRS can be aone-dimensional conveyor-belt based system. According to furtherembodiments disclosed (but not illustrated), the sample transportationsystem 10TRS can be a two-dimensional transportation system (such as amagnetic sample carrier transport system). The analytical laboratory 1can be configured to carry out the method according to the embodimentsdisclosed herein.

Turing now to FIGS. 2-5 , embodiments of the disclosed method ofoperating an analytical laboratory shall be described with reference tothe figures.

As shown on FIG. 2 , in a first preparatory step 100, a load limit canbe set for each laboratory instrument 10. The load limit can initiallybe set at a value equal to a maximum instrument capacity of therespective laboratory instrument 10. According to embodiments disclosedherein, the maximum instrument capacity can be set by a vendor,manufacturer, and/or operator, optionally considering a safety margin.The maximum instrument capacity as well as the load limit may beexpressed as a number of biological samples a laboratory instrument 10can process in a given time frame, such as, for example, samples perhour/day and the like. Achieving an effective processing rate of thelaboratory instruments 10 as close as possible to the maximum instrumentcapacity is the goal of the optimization by the laboratory middleware20.

Once the load limit is set, in step 102, the laboratory middleware 20can dispatch biological samples to laboratory instrument(s) 10 at adispatch rate not greater than the instrument load limit. If the numberof biological sample(s) in the analytical laboratory 1 overall that needprocessing by the respective laboratory instrument 10 is lower than theload limit, then, of course, the laboratory middleware 20 can dispatchbiological sample(s) at a rate lower than the load limit. The biologicalsamples can be dispatched to those laboratory instrument(s) 10, whichare configured to carry out at least one test order corresponding to therespective biological sample. Additionally, according to embodimentsdisclosed herein, the laboratory middleware 20 can check whetherrespective laboratory instrument 10 has all resources (such asconsumables, reagents, quality control) available and ready to processthe biological sample according to the corresponding test order.

Thereafter, not illustrated on the flowchart of FIG. 2 for clarity, thelaboratory instruments 10 can receive and identify the biologicalsample(s) dispatched thereto. Upon identifying the biological samples,each laboratory instrument 10 can send test order queries to thelaboratory middleware 20, the test order query comprising dataidentifying the biological sample. In other words, the laboratoryinstruments 10 can ask the laboratory middleware what test to perform onthe received biological sample(s). In response to the test orderqueries, the laboratory middleware 20 can transmit test orders to thelaboratory instruments 10 corresponding to the biological samplesidentified in the respective test order queries. A test order cancomprise data indicative of one or more processing steps to be carriedout on the biological sample. According to embodiments disclosed herein,the test orders can be retrieved from a data storage 22 such as, forexample, a database internal or communicatively connected to thelaboratory middleware 20.

The laboratory instruments 10 can then process the biological sample(s)according to the test orders sent to them by the laboratory middleware20.

The sequence of the laboratory instruments 10 receiving/identifyingbiological samples and querying the laboratory middleware 20, thelaboratory middleware 20 replying with the test order, and thelaboratory instruments 10 processing the biological samples can berepeated in the analytical laboratory 1.

Parallel thereto, in a step 104, the laboratory middleware 20 canmonitor the rate at which the plurality of laboratory instruments 10query the laboratory middleware 20 for test orders (referred tohereafter as query rate). Since the laboratory instruments 10 cannotprocess biological samples without a test order, the query rate can be adirect and reliable indication of the rate at which the laboratoryinstrument 10 processes biological samples at a given time. Hence, bymonitoring the query rate, in a step 106, the laboratory middleware 20can determine an effective flow rate corresponding to each laboratoryinstrument 10, the effective flow rate being indicative of the rate atwhich the laboratory instrument 10 processes biological samples.

The laboratory middleware 20 can then compare the effective flow rate ofeach laboratory instrument 10 with the dispatch rate of biologicalsamples to that laboratory instrument 10 (referred to hereafter as firstlaboratory instrument 10). If the effective flow rate of a firstlaboratory instrument 10 is lower than the dispatch rate to the firstlaboratory instrument 10, the laboratory middleware 20, in a step 109,can decrease its load limit (of the first laboratory instrument 10). Inother words, if the laboratory middleware 20 determines that the firstlaboratory instrument 10 is not able to process its workload (dispatchedsamples), it can reduce its load limit to avoid overloading theinstrument.

On the other hand, if the effective flow rate of the first laboratoryinstrument 10 is greater than or equal to the dispatch rate to the firstlaboratory instrument 10, the laboratory middleware 20, in a step 108,can increase the load limit for the first laboratory instrument 10.

The method and the system disclosed herein can be advantageous sinceadjusting the load limit of laboratory instruments 10 as a reaction totheir effective flow rate can avoid overloading, or underutilization.Furthermore, determining the effective flow rate by the laboratorymiddleware based on the test order queries received from the laboratoryinstruments 10 can be advantageous as it can be devoid of anyassumptions of performance and can be implemented even without anychange to the existing laboratory instruments 10.

Some embodiments of how the middleware 20 can determine the amount theload limit can be increased/decreased will be described with referenceto the sequence of FIGS. 3A-C.

FIG. 3A shows a simulation of a current prior art performance in oneparticular scenario where a laboratory instrument is processingbiological samples at its maximum instrument capacity for a considerableamount of time. The line 310 illustrates the dispatch rate to thelaboratory instrument. The line 320 illustrates the effective flow rateof the laboratory instrument.

The horizontal lines correspond to theoretical and physical limits ofsuch laboratory instruments. With the current prior art laboratorymiddleware, the performance output (effective flow rate) would becomedegraded over time because the laboratory instruments are sometimes notable to process biological samples at such a constant dispatch rate.This situation can become even more critical when a laboratoryinstrument needs to be temporarily stopped (for replacing a reagentcassette for example), since biological samples would accumulate and abacklog would arise, which could overload the laboratory instrument.

FIG. 3B, shows the effect of the disclosed method comprising increasingrespectively decreasing the load limit of a laboratory instrument 10 asa reaction to its effective flow rate. As illustrated in this figure,proactively decreasing the load limit of an instrument can preventoverloading, allowing the instrument to return closer to its maximumcapacity. On the other hand, increasing the load limit once theinstrument is again able to process samples at the rate they aredispatched can prevent underutilization of the instrument.

According to embodiments disclosed herein, the laboratory middleware 20can increase or decrease the load limit of the first laboratoryinstrument 10 using continuously modulated control such as, for example,a proportional-integral-derivative PID, a proportional-integral PI, aproportional-derivative PD, a proportional or an integral controlalgorithm. A continuously modulated control continuously (orquasi-continuously) can calculate an error value e(t) as the differencebetween a desired set point (SP) and a measured process variable (PV)and can apply a correction based on proportional, integral, andderivative terms (denoted P, I, and D respectively). The error value ecan be calculated by the laboratory middleware 20 as the differencebetween the effective flow rate and the maximum instrument capacity.From the variation of the error value e over time, an error curve e(t)can be determined.

In order to bring the effective flow rate of a laboratory instrument asclose as possible to its maximum instrument capacity, the laboratorymiddleware 20 can increase/decrease the load limit by a correction valuedetermined as a weighted sum of:

-   -   A proportional term P—The proportional term P can be calculated        as proportional to the error value e and can be indicative of        the magnitude of the error value e. The proportional response        can be adjusted by multiplying the error by a proportional gain.    -   An integral term I—The integral term I can be calculated as an        integral of the error curve e(t) over a period of time t and can        be indicative of the magnitude and duration of the error        value e. In other words, the contribution from the integral term        I can be proportional to both the magnitude of the error value e        and the duration of the error value e. The integral in a PID        controller can be the sum of the instantaneous error over time        and gives the accumulated offset that should have been corrected        previously. The accumulated error can then be multiplied by the        integral gain and added to the controller output. The advantage        of the integral term I can be that it can accelerate the return        of the performance (effective flow rate) of the process towards        its target (maximum instrument capacity) and can eliminate the        residual steady-state error that occurs with a pure proportional        controller.    -   A derivative term D—The derivative term D can be calculated as a        derivative of the error curve e(t) over a period of time t and        can be indicative of a rate of change of the error value e. The        derivative of the process error can be calculated by determining        the slope of the error over time and multiplying this rate of        change by the derivative gain. The magnitude of the contribution        of the derivative term D to the overall control action is termed        the derivative gain. Derivative action can predict system        behavior and thus can improve settling time and stability of the        system.

It can be noted that according to particular embodiments, one or more ofthe proportional gain; the integral gain; and/or the derivative gain maybe also zero. According to further embodiments disclosed herein, the oneor more of the proportional gain; the integral gain; and/or thederivative gain can be refined in view of the response of the system,namely the change of effective flow rate as a response to a change inthe load limit.

Turning now to FIGS. 4A-D, further embodiments of the disclosed methodwill be described.

FIG. 4A shows a first page of the multi-page flowchart showing steps 100through 109 (as described above) and off-page connectors A to C, eachoff-page connector being related to particular embodiments of actionstaken by the laboratory middleware 20 in response to the effective flowrate of laboratory instrument(s) 10 deviating from their respective loadlimits (the effective flow rate of the first laboratory instrument 10)is lower than the corresponding dispatch rate).

FIG. 4B shows the second page of the multi-page flowchart illustratingsteps from off-page connector A. In order to (re) distribute theworkload between laboratory instruments 10 (load balancing—step 110),the laboratory middleware 20 can determine a second laboratoryinstrument 10 of the plurality of laboratory instruments 10 (other thanthe first laboratory instrument 10) configured to carry out the sametest order corresponding to the respective biological sample as thefirst laboratory instrument 10. Having determined an alternativeinstrument to process the biological sample(s), in a step 110 a, thelaboratory middleware 20 can increase the load limit of the secondlaboratory instrument 10 by the difference between the effective flowrate and the dispatch rate of the first laboratory instrument 10. Toprevent the second laboratory instrument 10 from being overloaded, thelaboratory middleware 20 can increase the load limit of the secondlaboratory instrument 10 up to a value not greater than its maximuminstrument capacity. Additionally, or alternatively, in a step 110 b,the laboratory middleware 20 can adjust load balancing rule(s) of thelaboratory middleware 20 so to decrease the proportion of biologicalsamples dispatched to the first laboratory instrument 10 and increasethe proportion biological samples dispatched to the second laboratoryinstrument 10. A load balancing rule can define the proportion ofbiological samples sent to each laboratory instrument 10PRE, 10AI,10POST configured to carry out a particular test order. Thereafter, in astep 110 c, the laboratory middleware 20 can redirect samples from thefirst laboratory instrument 10 to the second laboratory instrument 10 ata rate equal to the difference between the effective flow rate and thedispatch rate of the first laboratory instrument 10. Additionally, oralternatively, the laboratory middleware 20 can dispatch biologicalsamples to the first laboratory instrument 10 and/or to the secondlaboratory instrument 10 according to the load balancing rule (asadjusted in step 110 b).

According to embodiments disclosed herein, in redirecting the biologicalsamples (load balancing), the laboratory middleware 20 can also takeinto consideration a transportation time of the biological sample(s) tothe laboratory instrument 10 the sample is redirected to. Thetransportation time can be the time required (estimated) to transportthe biological sample(s) from the first laboratory instrument 10 to thesecond laboratory instrument 10 either manually and/or by an automatedsample transportation system 10TRS. The calculation/estimation of thetransportation time can be based on data indicative of a layout of thesample transportation system 10TRS and/or data indicative of aneffective transportation capacity/availability of the sampletransportation system 10TRS or a specific transportation route of thesample transportation system 10TRS from the first to the secondlaboratory instrument. Overall, in optimizing the processing ofbiological sample(s), the laboratory middleware 20 can monitor andcontrol the load of the sample transportation system 10TRS similarly toother laboratory instruments 10, namely monitoring its effective flowrate and adjusting its load limit (in this case transportation capacity)to avoid overloading and/or underutilization of the sampletransportation system 10TRS. In such a way, the overall turn-around-timeTAT of the respective biological sample(s) can be significantly improvedby ensuring the biological sample(s) are transported to the laboratoryinstruments 10 as efficiently as possible.

FIG. 4C shows the third page of the multi-page flowchart illustratingsteps from off-page connector B. As illustrated on this figure,alternatively, or additionally, to load balancing (step 110), if theeffective flow rate of the first laboratory instrument 10 is lower thanthe corresponding dispatch rate, the laboratory middleware 20 can bufferbiological samples to temporarily reduce the workload of the laboratoryinstruments 10. In a first step, the laboratory middleware 20 candetermine whether any laboratory instrument 10 (referred hereafter asthird laboratory instrument) has available buffer capacity. Bufferingmay be provided either by laboratory instrument dedicated fortemporarily storing biological samples and/or by laboratory instruments10, which have available temporary storage space for biologicalsample(s) fulfilling the requirements (temperature, humidity) for samplebuffering. If there is available buffer capacity, in a step 112 a, thelaboratory middleware 20 can dispatch biological samples to the thirdlaboratory instrument 10 having available buffer capacity. Afterdispatching biological sample(s) for buffering, the laboratorymiddleware 20 can keep monitoring the effective flow rate of the firstlaboratory instrument 10 and—in a step 112 b—can dispatch biologicalsamples from the third laboratory instrument 10 to the first laboratoryinstrument 10 as soon as the effective flow rate of the first laboratoryinstrument 10 is equal to or greater than the corresponding dispatchrate. This way, biological sample(s) can be kept in a buffer only aslong as needed.

Similarly to load balancing, the laboratory middleware 20 can also takeinto consideration a transportation time of the biological sample(s) tothe third laboratory instrument 10 for buffering. In this way, it can beavoided that biological sample(s) are dispatched for buffering(temporary storage) for periods of time potentially shorter than thetime it can take the sample transportation system 10TRS to transport thesamples for buffering. Such embodiments can be advantageous since wasteof both buffering and transportation capacity can be prevented.

FIG. 4D shows the fourth page of the multi-page flowchart illustratingsteps from off-page connector C. FIG. 4D illustrates various methods ofa process called instrument masking. Instrument masking, in general, canrefer to the process of hiding a particular laboratory instruments 10from other instruments, as if it would not be available; would beoffline; and/or would not exist.

According to embodiments disclosed herein, instrument masking can beordered into two main categories: destination masking and input specificmasking.

Destination masking can refer to the process of preventing one or moreof the plurality of laboratory instruments 10 from sending biologicalsample(s) to the first laboratory instrument 10 (the destination).According to a first embodiment of destination masking (step 114 a),referred to as overall destination specific masking, masking cancomprise preventing one or more of the plurality of laboratoryinstruments 10 from sending any biological sample(s) to the firstlaboratory instrument 10.

In a further embodiment of destination masking, referred to as testspecific destination masking—step 114 b, masking the first laboratoryinstrument 10 can comprise preventing one or more of the plurality oflaboratory instruments 10 from sending any biological sample(s) havingat least one associated test order which the first laboratory instrument10 is configured to carry out.

Instrument masking can address the need for an analytical laboratory 1and method of operating an analytical laboratory 1 wherein anoverloading of the entire analytical laboratory 1 can be prevented.According to embodiments disclosed herein, preventing one or more of theplurality of laboratory instruments 10 from receiving biologicalsample(s) can comprise preventing (physically) even the loading of therespective biological sample(s) and/or automatically unloading thebiological sample(s), e.g., into an error output. Such embodiments canbe advantageous as they can limit the inflow of biological samples intothe analytical laboratory 1, thereby preventing that the overallanalytical laboratory 1 is overloaded, including buffer and archivingcapacity of the laboratory instruments 10.

The second category of instrument masking, input specific masking, canrelate to ensuring that the analytical laboratory 1 can still receiveand process urgent biological samples while still controlling theoverall load of the analytical laboratory 1. In order to achieve this,according to further embodiments, masking of laboratory instruments 10can be performed with respect to all laboratory instruments 10, otherthan one or more laboratory instruments 10 reserved for receivingbiological samples of high priority. Biological samples may beidentified as urgent either by a data marking the biological sample asurgent (STAT sample), the data being read from an identifying labelattached to a sample carrier and/or from a data storage unit 22, inparticular, as part of the corresponding test order. Alternatively, oradditionally, a particular sample tube can identify the biologicalsample(s) contained therein as urgent. Alternatively, or additionally,any biological sample(s) loaded into a particular laboratory instrumentmay be designated as urgent, in such case, the respective laboratoryinstrument being reserved for urgent samples only.

Within input specific masking, two embodiments can be distinguished:

-   -   1) Overall input specific masking 114 c, wherein one or more of        the plurality of laboratory instruments 10 other than the first        laboratory instrument 10 and other than one or more laboratory        instruments 10 reserved for receiving biological samples of high        priority are prevented from receiving any biological sample(s).    -   2) Test and input specific masking 114 d, wherein one or more of        the plurality of laboratory instruments 10 other than the first        laboratory instrument 10 and other than one or more laboratory        instruments 10 reserved for receiving biological samples of high        priority are prevented from receiving biological sample(s)        having at least one associated test order which the first        laboratory instrument 10 is configured to carry out.

In order to provide an overview of various embodiments of managing theworkload and resources of an analytical laboratory 1 by the laboratorymiddleware 20, FIG. 5 shows a flowchart illustrating load limit control,load balancing, sample buffering as well as instrument maskingprocesses.

Turning now to FIGS. 6-9 , particular embodiments of the laboratoryinstruments 10PRE, 10POST, 10AI are described.

FIG. 6 shows a pre-analytical laboratory instrument 10PRE comprising asample container sorting unit 14 configured to sort sample containers 30holding biological samples into sample racks 40, each sample rack 40being identified by a rack identifier of a rack tag 42 attached to thesample rack 40, the pre-analytical laboratory instruments 10PRE beingfurther configured to transmit signals to the laboratory middlewareassociating the sample identifier(s) ID of sorted sample containers 30with the sample rack identifier(s) of the corresponding sample rack(s)40. For embodiments where a pre-analytical laboratory instrument 10PREsorts sample containers 30 into sample racks 40, one or more analyticallaboratory instruments can be further configured to read the rackidentifier Rack-ID from the rack tag 42 and transmit the rack identifierRack-ID to the laboratory middleware with the test query.

FIG. 7 shows a further embodiment of a pre-analytical laboratoryinstrument 10PRE, comprising an aliquoting unit 16 configured to preparealiquots of biological sample(s) from the sample container(s) 30 andprovide each of the aliquots with a sample identifier ID on anidentifier tag 32 by an identifier tag writer 60.

FIG. 8 shows an embodiment of an analytical laboratory instrument 10AI,comprising an analytical unit 18 configured to carry out an analyticaltest to measure the presence, absence and/or concentration of at leastone analyte in the biological sample. The analytical laboratoryinstrument 10AI can perform analytical test(s) of the biological samplein response to the test order(s).

FIG. 9 shows an embodiment of a post-analytical laboratory instrument10POST comprising a sample storage unit 19. The post-analyticallaboratory instrument 10AI can be configured to store respectivelyretrieve sample containers 30 into respectively from the sample storageunit 19. The query by post-analytical laboratory instrument(s) 10POST tothe laboratory middleware for a processing order can comprise acontainer to store respectively retrieve into respectively from thesample storage unit 19. Correspondingly, when queried by apost-analytical laboratory instrument 10POST, the laboratory middlewarecan transmit data indicative of a sample container 30 to be retrievedfrom the sample storage unit 19. In response to the data indicative of asample container 30 to be stored respectively retrieved, thepost-analytical laboratory instrument 10POST can store respectivelyretrieves the sample container 30 from the sample storage unit 19.

Further disclosed is a computer program product comprising instructionswhich, when executed by a laboratory middleware 20 of an analyticallaboratory 1, can cause the analytical laboratory 1 to perform the stepsof any one of the methods disclosed herein. Thus, specifically, one,more than one or even all of method steps as disclosed herein may beperformed by using a computer or a computer network (such as a cloudcomputing service) or any suitable data processing equipment. As usedherein, a computer program product can refer to the program as atradable product. The product may generally exist in any format, such asin a downloadable file, on a computer-readable data carrier on premiseor located at a remote location (cloud). The computer program productmay be stored on a non-transitory computer-readable data carrier; aserver computer as well as on transitory computer-readable data carriersuch as a data carrier signal. Specifically, the computer programproduct may be distributed over a data network. Furthermore, not onlythe computer program product, but also the execution hardware may belocated on premise or in a remotely, such as in a cloud environment.

Further disclosed and proposed is a non-transitory computer-readablestorage medium comprising instructions which, when executed by alaboratory middleware 20 of an analytical laboratory 1, can cause theanalytical laboratory 1 to perform the steps of any one of the methodsdisclosed herein.

Further disclosed and proposed is a modulated data signal comprisinginstructions, which, when executed by a laboratory middleware 20 of ananalytical laboratory 1, can cause the analytical laboratory 1 toperform the steps of any one of the methods disclosed herein.

It is noted that terms like “preferably,” “commonly,” and “typically”are not utilized herein to limit the scope of the claimed embodiments orto imply that certain features are critical, essential, or evenimportant to the structure or function of the claimed embodiments.Rather, these terms are merely intended to highlight alternative oradditional features that may or may not be utilized in a particularembodiment of the present disclosure.

Having described the present disclosure in detail and by reference tospecific embodiments thereof, it will be apparent that modifications andvariations are possible without departing from the scope of thedisclosure defined in the appended claims. More specifically, althoughsome aspects of the present disclosure are identified herein aspreferred or particularly advantageous, it is contemplated that thepresent disclosure is not necessarily limited to these preferred aspectsof the disclosure.

We claim:
 1. A method of operating an analytical laboratory comprising alaboratory middleware communicatively connected to a plurality oflaboratory instruments configured to process biological samples, themethod comprising the steps of: setting a load limit by the laboratorymiddleware for each laboratory instrument at a value equal to a maximuminstrument capacity of the laboratory instrument; dispatching biologicalsamples by the laboratory middleware to laboratory instrument(s) at adispatch rate not greater than the instrument load limit, wherein thebiological samples are dispatched to laboratory instrument(s) configuredto carry out at least one test order corresponding to the biologicalsample; receiving and identifying biological samples by the laboratoryinstruments; sending test order queries by each laboratory instrument tothe laboratory middleware upon identifying a biological sample, the testorder query comprising data identifying the biological sample; inresponse to the test order queries, transmitting test orders by thelaboratory middleware to the laboratory instruments corresponding to thebiological samples identified in the test order queries; monitoring aquery rate of the plurality of laboratory instruments by the laboratorymiddleware in order to determine an effective flow rate corresponding toeach laboratory instrument; and in response to determining that theeffective flow rate of the first laboratory instrument is lower than thecorresponding dispatch rate, masking the first laboratory instrumentwith respect to one or more of the plurality of laboratory instrumentsother than the first laboratory instrument.
 2. The method of operatingan analytical laboratory according to claim 1, further comprising,checking whether each laboratory instruments have all resourcesavailable to process the biological sample according to the test order.3. The method of operating an analytical laboratory according to claim2, wherein resources comprise consumables, reagents, quality control,and combinations thereof.
 4. The method of operating an analyticallaboratory according to claim 1, further comprising, checking whethereach laboratory instruments is ready to process the biological sampleaccording the test order.
 5. The method of operating an analyticallaboratory according to claim 1, wherein masking the first laboratoryinstrument comprises preventing one or more of the plurality oflaboratory instruments from sending biological sample(s) to the firstlaboratory instrument.
 6. The method of operating an analyticallaboratory according to claim 5, wherein the biological sample(s) haveat least one associated test order, which the first laboratoryinstrument is configured to carry out.
 7. The method of operating ananalytical laboratory according to claim 5, wherein preventing one ormore of the plurality of laboratory instruments from sending biologicalsample(s) to the first laboratory instrument comprises preventingloading of the biological samples(s) and/or automatic unloading of thebiological sample(s).
 8. The method of operating an analyticallaboratory according to claim 1, wherein all laboratory instruments inthe plurality of laboratory instruments are masked except for one ormore laboratory instruments reserved for receiving biological samples ofhigh priority.
 9. The method of operating an analytical laboratoryaccording to claim 8, wherein biological samples of high priority areidentified as high priority by marking the biological sample as urgenton an identifying label attached to a sample carrier and/or a datastorage unit.
 10. The method of operating an analytical laboratoryaccording to claim 9, wherein the identifying label attached to a samplecarrier and/or a data storage unit is read as part of the test order.11. The method of operating an analytical laboratory according to claim8, wherein biological samples of high priority are identified as highpriority by particular sample tubes containing the biological samples.12. The method of operating an analytical laboratory according to claim8, wherein biological samples of high priority are identified as highpriority by loading the biological samples into the laboratoryinstruments reserved only for biological samples of high priority. 13.The method of operating an analytical laboratory according to claim 1,wherein the query rate comprises a number of distinct test order queriesreceived from a laboratory instrument in a set period of time.
 14. Themethod of operating an analytical laboratory according to claim 1,wherein the effective flow rate indicated rate at which the laboratoryinstrument processes biological samples.
 15. The method of operating ananalytical laboratory according to claim 1, further comprising,retrieving test orders by the laboratory middleware from a data storageunit based on the data identifying the biological sample.
 16. The methodof operating an analytical laboratory according to claim 1, wherein theplurality of laboratory instruments are interconnected by a sampletransportation system.
 17. The method of operating an analyticallaboratory according to claim 16, wherein the sample transportationsystem is a one-dimensional transportation system.
 18. The method ofoperating an analytical laboratory according to claim 17, wherein thesample transportation system is a two-dimensional transportation system.19. The method of operating an analytical laboratory according to claim1, wherein masking prevents overloading of the analytical laboratory.20. The method of operating an analytical laboratory according to claim1, wherein the plurality of laboratory instruments comprises one or moreof analytic instruments, pre-analytical instruments, or post-analyticalinstruments.